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Lymphoma

Primary testicular diffuse large B-cell lymphoma displays distinct clinical and biological features for treatment failure in rituximab era: a report from the International PTL Consortium

Leukemia volume 30, pages 361–372 (2016)Cite this article

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Abstract

Primary testicular diffuse large B-cell lymphoma (PT-DLBCL) is a unique subtype of DLBCL. The impact of rituximab on survival and patterns of treatment failure in PT-DLBCL patient remain controversial. We analyzed the clinical and biological feature of 280 PT-DLBCL cases, 64% of which were treated with rituximab-containing regimens. Although most (95%) patients achieved complete remission, a continuous risk of relapse was observed. Rituximab significantly reduced the cumulative risk of relapse (P=0.022) and improved both progression-free survival (PFS, P=0.012) and overall survival (OS, P=0.027) of PT-DLBCL patients (5-year PFS, 56% vs 36%; 5-year OS, 68% vs 48%). Central nervous system and contralateral testis were the most common sites of relapse, but other extranodal and nodal sites of relapse were also observed. Most cases of PT-DLBCL had a non-germinal center B-cell like (84%) immunophenotype and an activated B-cell like (86%) gene expression profile (GEP) subtype. The distinctive GEP signature of primary testicular lymphoma was relevant to tumor cell proliferation, dysregulated expression of adhesion molecules and immune response, likely accounting for the poor outcome. Accordingly, forkhead box P1 transcription factor (FOXP1) and T-cell leukemia/lymphoma 1 (TCL1) oncogenic activation were confirmed and predicted a significant trend of poor survival. This study provides valuable observations for better understanding of both clinical and biological features in PT-DLBCL patients.

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Acknowledgements

This study was supported by the National Cancer Institute/National Institutes of Health (R01CA138688 and 1RC1CA146299 to YL and KHY). KHY is supported by The University of Texas MD Anderson Cancer Center Lymphoma Moonshot Program, Institutional Research and Development Fund, an Institutional Research Grant Award, an MD Anderson Cancer Center Lymphoma Specialized Programs on Research Excellence (SPORE) Research Development Program Award, an MD Anderson Cancer Center Myeloma SPORE Research Development Program Award and the Gundersen Lutheran Medical Foundation Award, and is partially supported by the National Cancer Institute/National Institutes of Health (P50CA136411 and P50CA142509). GCM is supported by a grant from the Michael and Susan Dell Foundation. Dr Xu-Monette is the recipient of the Shannon Timmins Leukemia Fellowship Award at The University of Texas MD Anderson Cancer Center. KHY also receives research support from Roche Molecular System, Gilead Sciences Pharmaceutical, Seattle Genetics, Dai Sanyo Pharmaceutical, Adaptive Biotechnology, and HTG Molecular Diagnostics.

Author contributions

LD, ZYX-M, SL and KHY designed study, conducted the research and performed the statistical analysis; LD, ZYX-M, SL, GCM, YX, CV, JH, LZ, QZ, YW, LQ, KD, AC, AMP, SZ, AT, HR, JA, ARS, MX, EDH, JZ, MP, SW, MZ, AJMF, BMP, YL, MAP, LJM and KHY contributed vital new reagents, resources, technology and analytical tools; LD, ZYX-M, SL, GCM, YX, CV, JH, LZ, QZ, YW, LQ, KD, AC, AMP, SZ, AT, HR, JA, ARS, MX, EDH, JZ, MP, SW, MZ, AJMF, BMP and KHY collected clinical and follow-up data under approval by the institutional review boards and the material transfer agreement; LD, LJM and KHY edited the manuscript; and all authors contributed vital strategies, participated in discussions and provided scientific input.

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Author notes

  1. L Deng: LD is the recipient of Hematology/Oncology Scholarship Award.

Authors and Affiliations

  1. Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    L Deng, Z Y Xu-Monette, S Loghavi, Y Xia, L J Medeiros & K H Young

  2. Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    G C Manyam & L Zhang

  3. San Bortolo Hospital, Vicenza, Italy

    C Visco

  4. Asan Medical Center, Ulsan University College of Medicine, Seoul, Korea

    J Huh

  5. Tianjin Medical University Cancer Institute and Hospital, Institute of Hematology, CAMS & PUMC, Tianjin, China

    Q Zhai, Y Wang & L Qiu

  6. Aalborg University Hospital, Aalborg, Denmark

    K Dybkær

  7. Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    A Chiu

  8. University of Manitoba, Winnipeg, MB, Canada

    A M Perry

  9. Indiana University School of Medicine, Indianapolis, IN, USA

    S Zhang

  10. University Hospital, Basel, Switzerland

    A Tzankov

  11. Sun Yat-Sen University Cancer Center, Guangzhou, China

    H Rao

  12. Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

    J Abramson & A R Sohani

  13. Yale University School of Medicine, New Haven, CT, USA

    M Xu

  14. Cleveland Clinic, Cleveland, OH, USA

    E D Hsi & Y Li

  15. Peking University Cancer Hospital and Institute, Beijing, China

    J Zhu

  16. San Raffaele H Scientific Institute, Milan, Italy

    M Ponzoni & A J M Ferreri

  17. National University Hospital, Singapore, Singapore

    S Wang

  18. The First Affiliated Hospital of Zhengzhou University, Henan, China

    Ling Li & M Zhang

  19. Gundersen Medical Foundation, La Crosse, WI, USA

    B M Parsons

  20. Hospital Universitario Marques de Valdecilla, Santander, Spain

    M A Piris

  21. The University of Texas School of Medicine, Graduate School of Biomedical Sciences, Houston, TX, USA

    K H Young

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  1. L Deng
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  29. Y Li
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  32. K H Young
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Correspondence to K H Young.

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Deng, L., Xu-Monette, Z., Loghavi, S. et al. Primary testicular diffuse large B-cell lymphoma displays distinct clinical and biological features for treatment failure in rituximab era: a report from the International PTL Consortium. Leukemia 30, 361–372 (2016). https://doi.org/10.1038/leu.2015.237

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